Lucentis Trial Patients: Seven Years Later
For many, vision has deteriorated.
■ A fascinating study that brought back 65 patients who participated in two of the earliest trials for Lucentis after seven years demonstrates a wide range of visual outcomes for these individuals, many of whom are now in their mid-80s. The study will be presented at the upcoming ARVO meeting in early May. Thus, this article will not go into specific detailed findings of the report.
The study, called Seven/Up and led by Robert B. Bhisitkul, MD, of the Department of Ophthalmology, University of California at San Francisco, involves patents who were originally enrolled in Genentech's pivotal ANCHOR and MARINA trials in 2003 and 2004. The 65 patients were part of a group that was then followed through the HORIZON extension study.
Once this cohort of early Lucentis patients was identified last year, they were re-evaluated with a complete battery of tests for retinal disease, including the most up-to-date SDOCT imaging.
What the researchers found was that at seven to eight years removed from their initial Lucentis injections, the patients could be divided into several distinct subgroups ranging from good vision (20/40 or better) and durable CNV quiescence, to a larger group with poor vision (20/200 or worse) and ongoing exudative disease activity. There were even several instances of patients who were legally blind (20/200 or worse in both eyes).
The researchers concluded that with these earliest Lucentis patients, clinical vigilance and prolonged treatment may be required in some patients for seven years or longer.
Alcon Buys International Ocriplasmin Rights
ThromboGenics to focus on US market.
■ ThromboGenics NV has entered into an agreement with Alcon for the commercialization of ocriplasmin, a pharmacologic therapy for vitreomacular adhesion (VMA) including macular hole, in all markets outside the United States. ThromboGenics will now concentrate on commercializing ocriplasmin in the US, where it plans to build its commercial and medical organization to support the product's anticipated launch within the next 12 months. Ocriplasmin has been granted priority review status by the FDA.
Under the terms of the agreement with Alcon, ThromboGenics will receive an upfront payment of 75 million euros, with a further 90 million euros in potential near-term milestone payments. Additional longer-term milestones are also possible and ThromboGenics will receive royalties on net sales of ocriplasmin. In addition to granting international rights for ocriplasmin, the agreement specifies that Alcon and ThromboGenics will work together, and share the costs, of developing new clinical applications of the product that the companies will introduce in their respective territories.
ThromboGenics has completed an extensive clinical development program, including two successful phase 3 studies that have shown that ocriplasmin could play an important role in treating symptomatic VMA including macular hole.
Members of the international retina community have already shown great interest in ocriplasmin, as it could for the first time provide them with a pharmacological option to treat patients with symptomatic VMA including macular hole. The availability of ocriplasmin may also enable retina specialists to treat patients earlier than they do with surgery. This could address a significant unmet need as earlier intervention has been shown to limit the progress of the disease and its related complications.
ASRS Letter on Fungal Endophthalmitis Cases
Single lot of Brilliant Blue suspected.
■ The following letter was sent to ASRS members in March after nine incidents of fungal endophthalmitis were reported following use of the intraoperative dye Brilliant Blue in vitrectomies.
“(In early March), an ASRS member notified the Therapeutic Surveillance Subcommittee of nine cases of suspected fungal endophthalmitis following Brilliant Blue G (BBG)-assisted vitrectomy procedures. All cases were performed at an ASC.
After reviewing the cluster of endophthalmitis cases, a common characteristic among all of the procedures was the use of BBG from a single lot. The cases involved two different retina groups and were done over a period of two months. In all cases, the BBG was compounded by the same pharmacy. The pharmacy conducted a rigorous investigation and cultured Fusarium from the unused vials returned by the ASC. The source of the fungus, however, has not been determined. There were no positive cultures from the original lot, and the pharmacy has reported that the compounding was performed under a septic conditions. The pharmacy voluntarily re-called all BBG from the same lot of the stock solution and is in the process of obtaining and performing microbiologic cultures. The pharmacy dispensed vials or syringes to 19 other physicians. The pharmacy contacted the 19 other physicians and no other ad verse events or instances of fungal endophthalmitis were reported, nor have any other cases of endophthalmitis been reported from other vials in this lot or any other lots.”
AAO Offers Guidelines for Genetic Testing
Family history is key to ordering tests.
■ The American Academy of Ophthalmology now believes that genetic testing has advanced to the point where ophthalmologists can employ such tests in certain circumstances as a means to achieve more accurate diagnoses and to alert patients to potential ocular problems.
In recently released guidelines for genetic testing, the Academy states that “genetic testing can make a very positive impact on individuals and families affected with inherited eye disease in a number of ways. When properly performed, interpreted and acted upon, genetic tests can improve the accuracy of diagnoses and prognoses, improve the accuracy of genetic counseling, reduce the risk of disease occurrence or recurrence in families at risk, and facilitate the development and delivery of mechanism-specific care.”
But the Academy cautions that “like all medical interventions, genetic testing has some specific risks that vary from patient to patient. For example, the results of a genetic test can affect a patient's plans to have children, create a sense of anxiety or guilt, and even perturb a patient's relationships with other family members.”
For these reasons, the Academy advises that professional counseling should be provided to all individuals who undergo genetic testing to maximize the benefits and minimize the risks associated with each test.
Following are the AAO's suggested guidelines for such testing:
► Offer genetic testing to patients with clinical findings suggestive of a Mendelian disorder whose causative genes have been identified. If unfamiliar with such testing, refer the patient to a physician or counselor who is. In all cases, ensure that the patient receives counseling from a physician with expertise in inherited disease or a certified genetic counselor.
► Use Clinical Laboratories Improvement Amendment (CLIA)-approved laboratories for all clinical testing. When possible, use laboratories that include in their reports estimates of the pathogenicity of observed genetic variants that are based upon a review of the medical literature and databases of disease-causing and non disease-causing variants.
► Provide a copy of the genetic test reports to the patients so that they will be able to independently seek mechanism-specific information, such as the availability of gene-specific clinical trials, should they wish to do so.
► Avoid direct-to-consumer genetic testing and discourage patients from obtaining such tests themselves. Encourage the involvement of a trained physician and/or genetic counselor for all genetic tests so that appropriate interpretation and counseling can be provided.
► Avoid unnecessary parallel testing. Order the most specific test(s) available given the patient's clinical findings. Restrict massively parallel strategies like whole-exome sequencing and whole-genome sequencing to research studies conducted at tertiary care facilities.
► Avoid routine genetic testing for genetically complex disorders like age-related macular degeneration and late-onset primary open-angle glaucoma until specific treatment or surveillance strategies have been shown in one or more published clinical trials to be of benefit to individuals with specific disease-associated genotypes. In the meantime, confine the genotyping of such patients to research studies.
► Avoid testing asymptomatic minors with untreatable disorders except in extraordinary circumstances. For the few cases in which such testing is felt to be warranted, the following steps should be taken before the test is performed: (a) the parents and child should undergo formal genetic counseling, (b) the certified counselor or physician performing the counseling should state his or her opinion in writing that the test is in the family's best interest, and (c) all parents with custodial responsibility for the child should agree in writing with the decision to perform the test.
|■ Genentech offers Lucentis “discount.” Retina practices purchasing Lucentis under the Lucentis Direct program may now be entitled to a larger discount on the drug through a modified program initiated in January.|
The new “discount” brings the price of the wet AMD drug down from $1,950 a dose to approximately $1,903 a dose. A Genentech spokes-person said the “list price” for Lucentis has not changed and remains at $1,950.
“Our programs are periodically reviewed and updated and we have made some modifications in the structure of the discount program,” said the Genentech spokesperson.
■ ASRS to gather post-market incident reports. The American Society of Retina Specialists said it is initiating a post-market surveillance committee through which retina specialists can report post-market incidents that occur with FDA-approved ophthalmic drugs and devices.
Pravin Dugel, MD, who is chairing the post-market committee, told Retinal Physician that retina specialists should feel comfortable in reporting these incidents to their peers. Of course, serious incidents will be reported to the ASRS and the FDA as well.
“We are working on a process that will include the ability to report these incidents online using a spreadsheet that we are developing,” said Dr. Dugel. “We intend to issue a quarterly report on these incidents and hope to identify any trends that could impact patient safety. We will work with the FDA and industry to ensure that this much-needed information can then be used in a positive and productive manner.”
■ Promising trial for RP drug. QLT Inc. said it had positive preliminary results from its international multi-center phase 1b proof-of-concept clinical trial of QLT091001 for the treatment of retinitis pigmentosa (RP) due to inherited genetic mutations in retinal pigment epithelium protein 65 or lecithin retinol acyltransferase (LRAT).
The phase 1b study showed rapid, statistically significant and clinically meaningful changes in visual fields from baseline values as well as improvements in visual acuity in the study of 17 RP subjects. Nine of 17 subjects (53%) showed an improvement in VA over baseline in at least one eye by greater than or equal to five ETDRS letters.
In addition, small subsets of RP subjects were investigated for secondary effects on other key vision parameters impacted by RP, such as decreased retinal sensitivity, and the data available in these subsets showed notable and promising increases in average sensitivity levels. The single-course treatment data with QLT091001 represents the first stage of dose-regimen testing as the basis for a longer term multiple course regimen in RP due to mutations in RPE65 and LRAT.
■ Endophthalmitis after anti-VEGF injection. Bascom Palmer Eye Institute, which has been constantly updating its database covering years of in-house anti-VEGF injections, recently reported on the statistics for endophthalmitis incidence for more than 75,000 injections.
The data, which covers the anti-VEGF injections performed at Bascom Palmer between January 1, 2005, and December 31, 2010, identified 13 endophthalmitis-suspect cases, of which eight were culture-positive. Five of these cases were linked to Streptococcus bacteria and were also associated with the poorest visual outcomes. These results were presented by Andrew Moshfeghi, MD, at the recent Angiogenesis meeting at Bascom Palmer. RP